The objective of this project is to develop a sensor platform that will enable a wide variety of electrochemical sensors to survive long-term implantation in the body. In spite of considerable effort that has gone into developing indwelling sensors, current implanted sensors are not capable of providing reliable data for long periods of time. It is believed that the unstable responses seen in these sensors are due in large part to the body's inflammatory response to the sensor. This response causes initial loss of sensor sensitivity, instability over time, signal drift, and uncorrelated signal variations. The main cause of signal instability and drift is the formation of a nonvascular capsule around the sensor that significantly modifies the availability of any analyte on the sensor surface. If the capsule is removed, the sensor returns to its original response, indicating that the sensor itself is working after implantation for several months. The goal of the proposed R21 research is to solve the problem of nonvascular capsule formation on an implanted electrochemical device by controlling the microarchitecture of the device. The results will then lead to the development of a variety of sensors that will give a more stable and accurate response. SRI has already shown in collaboration with a commercial client that a passive device with a controlled grid structure shows a reduced inflammatory response, even when it is implanted for a period of 3 weeks. The goal is to apply the results of this research to the construction of an electrochemical sensor that uses the grid itself as the substrate so that the sensor will maintain the architecture of the grid substrate. To prove the concept, SRI has chosen an oxygen sensor for development. Monitoring of tissue oxygen has been proven to have many roles in physiology and medicine. In addition to application in cardiopulmonary physiology, knowledge of tissue oxygen tension gives valuable information about intravascular volume status and neurological function. In the proposed study, SRI will create an oxygen sensor in a plastic material with approximately 18 (nine 3-dimensional and nine 2-dimensional) carefully controlled grid structures, implant them in rats, and monitor the electrochemical signal for a period of 2-3 months. The sensor will also be inspected microscopically to evaluate any capsular formation. The proposed work will lay the foundation for developing several other sensors that can be implanted in humans for real-time monitoring of clinically important species.